Insecticidal compositions and methods of combatting insects using phosphorylated 1,2,5-thiadiazoles

ABSTRACT

INSECTICIDAL COMPOSITIONS AND METHODS OF KILLING INSECTS USING PHOSPHORYLATED 1,2,5-THIADIAZOLES.

United States Patent O M INSECTICIDAL COMPOSITIONS AND METHODS OFCOMBATTING INSECTS USING PHOSPHO- RYLATED 1,2,5-THIADIAZOLES Michael D.Barker, Maidstone, England, and Peter Kirby, Modesto, Calif., assignorsto Shell Oil Company, New York, N.Y.

No Drawing. Original application Apr. 12, 1968, Ser. No. 721,088, nowPatent No. 3,666,768, dated May 30, 1972. Divided and this applicationJan. 20, 1972, Ser. No. 219,561

Claims priority, application Great Britain, Apr. 14, 1967,

17,199/ 67 Int. Cl. A01n 9/36 US. Cl. 424-200 18 Claims ABSTRACT OF THEDISCLOSURE Insecticidal compositions and methods of killing insectsusing phosphorylated 1,2,5-thiadiazoles.

BACKGROUND OF THE INVENTION Field of the invention This is a division ofapplication Ser. No. 721,088 filed Apr. 12, 1968, now US. Pat. 3,666,768issued May 30, 1972. This invention relates to novel phosphorylated1,2,5- thiadiazoles, having a high level of insecticidal activity.

Description of the prior art DESCRIPTION OF THE PREFERRED EMBODIMENTSThe novel compounds of this invention can be described by the generalformula wherein X is oxygen or sulfur; R is hydrogen, halogen, cyano,alkoxycarbonyl carbamoyl, N-alkyl or N,N-dialky1- carbamoyl, or ahydrocarbon group which is an alkyl, cycloalkyl, aryl, alkaryl oraralkyl or such a hydrocarbon group substituted by from one to aplurality of halogen or cyano substituents; and R and R which may be thesame or different, are alkyl.

Any halogen substituents, i.e., fluorine, chlorine, bromine or iodine,present are preferably middle halogen, i.e., chlorine or bromine.

The alkoxycarbonyl groups suitably contain 2-7, preferably 2-5, carbonatoms, and include methoxycarbonyl, ethoxycarbonyl, isoproxycarbonyl,propoxycarbonyl, butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl andthe like.

Each alkyl group in the 'N-alkyl or N,N-dialkylcarbamoyl- 3,729,557Patented Apr. 24, 1973 where each R is hydrogen or alkyl of 1-6 carbonatoms group suitably has from 1-6, preferably 1-4, carbon atoms, andinclude methyl, ethyl, propyl, isopropyl, isobutyl, pentyl, hexyl andthe like.

When R is alkyl, it is suitably of 1-6, preferably 1-4, carbon atoms,and includes methyl, ethyl, propyl, isobutyl, pentyl, hexyl and thelike.

When R is cycloalkyl, it suitably has from 3-8 carbon atoms in the ringwith 3-6 preferred and includes cyclopropyl, cyclobutyl, cyclohexyl,cyclooctyl and the like.

When R is aryl, it is suitably of 6-10, preferably 6, carbon atoms.

Suitable aralkyl and alkaryl radicals are those having 7-18, preferably71(), carbon atoms.

Examples of suitable aryl, aralkyl and alkaryl radicals are phenyl,naphthyl, benzyl, phenethyl, phenylisopropyl, 4-tolyl,2,4,6-trimethylphenyl and the like.

It is understood that any of the alkyl moieties of R, R or R may bebranched or straight-chain.

When the hydrocarbon groups are substituted by halogen or cyano, thenumber of these substituents is suitably up to three, preferably one.

The alkyl radicals represented by R, and R suitably have from 1-6,preferably 1-4, carbon atoms, and include methyl, ethyl, propyl,isopropyl, butyl, isobutyl, pentyl, hexyl and the like.

Within the phosphorylated 1,2,5-thiadiazoles of Formula I, it appearsthat the species having the highest insecticidal activity are those ofthe subclass where X is oxygen or sulfur, R is hydrogen and R and R areeach alkyl of l4 carbon atoms. This subclass thus is preferred.

The preferred species within this subclass are:

dimethyl 1,2,5-thiadiazol-3-yl phosphorothionate diethyl1,2,5-thiadiazol-3-yl phosphorothionate methyl isopropyl1,2,5-thiadiazol-3-yl phosphorothionate methyl butyl1,2,5-thiadiazol-3-yl phosphorothionate diethyl1,2,5-thiadiazo1-3-y1phosphorate.

The compounds of this invention are effective against a broad spectrumof insects. By the term insect is meant not only those members of theclass Insecta, but also related or similar non-vertebrate animalorganisms belonging to the allied classes of arthropods and includingmites, ticks, spiders, wood lice and the like.

The compounds of this invention may be used in the form of pesticidalcompositions. The pesticidal compositions contain the conventional inertcarriers, i.e., the liquid or solid agents normally associated withpesticides. The pesticidal compositions may also include surface activeagents.

The term carrier as used herein means a material,

which may be inorganic or organic and of synthetic or natural origin,with which the active compound is mixed or formulated to facilitate itsapplication to the plant, seed, soil or other object to be treated, orits storage, transport-or handling. The carrier may be a solid or a.fluid. Any of the material usually applied in formulating pesticides maybe used as carrier.

Examples of suitable solid carrier are silicates, clays, for example,kaolinite clay, synthetic hydrated silicon oxides, synthetic calciumsilicates, elements such as for example, carbon and sulfur, natural andsynthetic resins such as for example, coumarone resins, rosin, copal,shellac, dammar, polyvinyl chloride and styrene polymers and copolymers,solid polychlorophenols, bitumen, asphaltite, Waxes such as for example,beeswax, parafiin wax, montan wax and chlorinated mineral waxes, andsolid fertilizers for example, superphosphates.

Examples of suitable fluid carriers are water, alcohols, such as forexample, isopropanol, ketones such as for example, acetone, methyl ethylketone, methyl isobutyl ketone and cyclohexanone, ethers, aromatichydrocarbons such as for example, benzene and toluene, petroleumfractions such as for example, kerosene, chlorinated hydrocarbons, suchas for example, carbon tetrachloride, including liquefied normallyvaporous gaseous compounds. Mixtures of different liquids are oftensuitable.

The surface-active agent may be a wetting agent, an emulsifying agent ora dispersing agent; it may be nonionic or ionic. Any of thesurface-active agents usually applied in formulating herbicides orinsecticides may be used. Examples of suitable surface-active agents arethe sodium or calcium salts of polyacrylic acids, the condensationproducts of fatty acids or aliphatic amines or amides containing atleast 12 carbon atoms in the molecule with ethylene oxide and/orpropylene oxide; partial esters of the above fatty acids with glycerol,sorbitan, sucrose or pentaerythritol; condensation products of alkylphenols, for example p-octylphenol or p-octylcresol, with ethylene oxideand/or propylene oxide; sulfates or sulfonates of these condensationproducts; and alkali metal salts preferably sodium salts, or sulfuricacid esters or sulfonic acids containing at least carbon atoms in themolecule, for example, sodium lauryl sulfate, sodium secondary alkylsulfates, sodium salts of sulfonated castor oil, and sodium alkylarylsulfonates such as sodium dodecylbenzene sulfonate.

The compositions of the invention may be formulated as wettable powders,dusts, granules, solutions, emulsifiable concentrates, emulsions andpastes. Wettable powders are usually compounded to contain 25, 50 or 75%of toxicant and usually contain, in addition to solid carrier, 310% of adispersing agent and, where necessary, 010% of stabilizer(s) and/ orother additives such as penetrants or stickers. Dusts are usuallyformulated as a dust concentrate having a similar composition to that ofa Wettable powder but without a dispersant, and are diluted in the fieldwith further solid carrier to give a composition usually containing/2-10% of toxicant. Granules are usually prepared to have a size between10 and 100 ES. mesh, and may be manufactured by agglomeration orimpregnation techniques. Generally, granules will contain /225% toxicantand 0-25% of additives such as stabilizers, slow release modifiers,binding agents, etc. Emulsifiable concentrates usually contain, inaddition to the solvent and, when necessary, co-solvent, 10-50% W./v.toxicant, 2-20% w./v. emulsifiers and 020%': of appropriate additivessuch as stabilizers, penetrants and corrosion inhibitors. Pastes arecompounded so as to obtain a stable, fiowable product and usuallycontain 10-60% toxicant, 220% of appropriate additives and, as carrier,water or an organic liquid in Which the toxicant is substantiallyinsoluble.

The compositions of the invention may contain other ingredients, forexample, protective colloids such as gelatin, glue, casein, gums andpolyvinyl alcohol; sodium polyphosphates; cellulose ethers, stabilizerssuch as ethylene diamine tetra-acetic acid; other pesticides; andstickers, for example, non-volatile oils.

Aqueous dispersions and emulsions, for example, compositions obtained bydiluting a wettable powder or an emulsifiable concentrate according tothe invention with water, also lie within the scope of the presentinvention. The said emulsions may be of the water-in-oil or of theoil-in-water type, and may have a thick mayonnaiselike consistency.

The amount of the 1,2,5-thiadiazole necessary to control or kill theinsects is defined as the pesticidal amount. This quantity willobviously vary with the species of 1,2,5- thiadiazole, the particularpest, type of formulation, environmental conditions, etc. Those versedin the insecticidal field, however, can readily determine the optimumamount for any particular situation.

The pesticidal composition will usually contain from about 0.00195% byweight of the 1,2,5-thiadiazole, based upon the total weight of1,2,5-thiadiazole and carrier.

The compounds of this invention may be prepared by a process whichcomprises reacting, preferably under basic conditions, ahydroxyl-l,2,5-thiadiazole of the following general formula I lwi N N ps (II) or an alkali metal salt thereof, with a halide of the followinggeneral formula R20 (II wherein R, R R and X have the meanings aforesaidand hal represents a halogen atom. The basic conditions for the reactionmay be produced Where necessary by the addition of a base. When a baseis added it may be a nitrogenous base, e.g. trimethylamine, orpreferably an alkali or alkaline earth metal carbonate, e.g. sodium orpotassium carbonate.

The reaction is preferably carried out in an inert liquid reactionmedium, which may be a solvent for the reactants or for the products ofthe reaction, or both. Inert reaction media such as acetone and methylisobutyl ketone are especially suitable for this purpose; other reactionmedia such as benzene, diethyl ether, and tetrahydrofuran may also beused.

The reaction may be carried out at a temperature in the range 0150 C.,preferably between 50 and 100 C.

The hydroxy-l,2,5-thiadiazoles used as starting materials in the aboveprocess may be prepared according to the method of Ross and Smith(Journal of the American Chemical Society, 1964, page 2861) or themethod of Weinstock et al. (Tetrahedron Letters 1966, page 1263), or bymodifications of these methods. When the group R in the hydroxy compoundof Formula II represents a N-alkyl or N,N-dialkylcarbarnoyl group, it isconveniently prepared by hydrolysis of3-hydroxy-4-cyano-l,2,S-thiadiazole, suitably by means of an alkalimetal hydroxide, followed by halogenation, conveniently using thionylchloride, and reaction of the resultant acyl halide with the appropriatealkyl or dialkylamine, preferably in ether solution.

The compounds of the invention, their preparation, their insecticidalactivity and compositions containing them are further illustrated in theexamples which follow. In Examples IV, which illustrate the preparationof certain compounds of this invention, the structure of the product wasconfirmed by NMR and IR analyses in addition to the elemental analysesfor which results are given. All the elemental analyses are based onpercent by weight.

EXAMPLE I Preparation of dimethyl 1,2,5-thiadiazol- 3-ylphosphorothionate Dry powdered potassium carbonate (1.4 g.) and dimethylphosphorochloridothionate (1.6 g.) were added to a solution of4-hydroxy-1,2,5-thiadiazole (1.0 g.) in dry methyl isobutyl ketone (15ml.) and the mixture stirred at -100 C. for 2 hours. After cooling, thereaction mixture was filtered and the solvent was removed from thefiltrate under reduced pressure. The residual oil obtained in thismanner was purified on a silica gel column using petroleum ether (B.P.4060 C.) as eluent.

The required compound was obtained as a yellow oil. Analysis.-C H PN;;SO requires (percent): C, 21.3; H, 3.1; P, 13.7. Found (percent): C,21.4; H, 3.1; P, 13.7.

EXAMPLE II Preparation of dimethyl 3-phenyl-1,2,5-thiadiazol- 4-ylphosphorothionate S OCH:

Cells-Ill EO-i OCH;

ing solid was then refluxed with thionyl chloride (34 ml.); after whichexcess thionyl chloride was distilled off under reduced pressure. Theresidue was dissolved in dry ether and anhydrous dimethylamine (0.1mole) dissolved in dry ether was added, the temperature being maintainedbetween 5-l0 C. The ether layer was then evaporated and the residuechromatographed on a silica gel column using chloroform/methanol aseluent and sublimed to yield 3-hydroxy-4-N,N-dimethylcarbamoyl 1,2,5thiadiazole.

This hydroxy-thiadiazole was then phosphorylated by a procedure similarto that described in Example II to yield the desired phosphorylatedproduct as an oil.

Analysis.-C H PN S O requires (percent), C, 28.3; H, 4.1; N, 14.1; P,10.4. Found (percent): C, 29.1; H, 4.1; N, 14.7; P, 9.3.

EXAMPLE V Following procedures analogous to those described in ExamplesI-IV, further phosphorylated 1,2,5-thiadiaz0les were synthesized andtheir analytical data are set out in Table 1 below The first compoundwas obtained as a solid, M.P. 4041' C., but the remainder of thecompounds were oils whose structure was deduced from the method ofsynthesis and confirmed by NMR and IR analyses.

In this Table 1, compounds are identified by reference to thesubstituents on the formula leum ether as eluent to yield the requiredcompound as R1 a colorless oil. R0-P Analysis.C H PN S O requires(percent) C, R2 39.8; H, 3.6; N, 9.3. Found (percent): C, 40.6; H, 3.8;N N

TABLE 1 Analysis (percent) Compound Req. Found R R1 R, X 0 H N P 01 0 HN P 01 H CH3 CH3 S CeHcPNzS 20s 25. 4 3. 2 10. 9 25. 7 2. 9 10. 8 CHaOC- CN CH3 CH3 S osHsPNaS 20a 23. 9 2. 4 16. 7 23. 8 2. 7 16. 2 01 0H;0113 S CAHBPNZS 20 01 18. 4 2. 3 10.8 18.6 2. 3 10.7 CH; CH3 CH3 scsHgPNzsgos 25. 0 3. 7 11.7 27. 4 3. 9 11.8 H 02H, 02H; s CsHllPNzS 032a. 4 4. 3 11.0 29. 2 4. 4 11.4 H CH3 CH(CH3)2 S CeHnPNzSzOz 28.4 4.328.2 4.3 H CH3 (CH2):CHz S C H PNzSzO 31. 3 4. 9 10.4 32. 2 5. 0 10.9CH: CzHs C211 0 C1H13PN2S O4 33. 3 5. 2 11. 1 32. 6 5. 1 10. 2

EXAMPLE HI EXAMPLE VI Preparation of diethyl 1,2,5-thiadiazol-3-ylphosphorate (I) OOzHs Following a similar procedure to that described inExample II, but replacing the dimethyl phosphorochlo- EXAMPLE IVPreparation of dimethyl 3-N,N-dimethylcarbamoyl- 1,2,5-thiadiazol-4-ylphosphorothionate 3-hydroxy-4-cyano-1,2,5-thiadiazole (0.04 mole) wasrefluxed with water (50 ml.) and potassium hydroxide (0.08 mole) for 4hours, the reaction mixture acidified, extracted with ether, dried andevaporated.. The result- Preparation of a wettable powder composition Awettable powder having the composition shown below was prepared byblending, hammer milling and air milling the components.

Percent Dimethyl 3-methoxycarbonyl 1,2,5 thiadiazol-4-ylphosphorothionate 25 Tamol 731 3 Empicol LZ 2 Microcel 8E 70 Where Tamol731 (registered trademark) is a sodium polyacrylate; Empicol LZ(registered trademark) is sodium laurylsulfate; and Microcel 8E(registered trademark) is a synthetic calcium silicate.

EXAMPLE VII Insecticidal activity of phosphorylated 1,2,5-thiadiazolesbrushed olf on the ventral abdomen of each, 20 flies being treated. Thetreated flies were held for 24 hours in glass jars, each containing alittle granulated sugar as food for the flies, and the percentage ofdead and moribund individuals was then recorded.

(II) A quantity of 0.1 ml. of a 0.1% by weight solution of the compoundto be tested in acetone was mixed in a beaker with 100 ml. of water.Twenty 6 day-old (4th instar) mosquito larvae (A edes aegypti) wereadded and the beakers stored for 24 hours. The percentage of dead andmoribund larvae was then recorded.

(Ill) The compounds were formulated as solutions or suspensions in watercontaining by weight of acetone and 0.05% by weight of Triton X 100' aswetting agent. The formulations contained 0.2% by weight of the compoundto be tested. Turnip and broad bean plants, trimmed to one leaf each,were sprayed on the under surface of the leaf with the aboveformulation. Spraying was effected with a spraying machine deliveringgallons per acre, the plants passing under the spray on a moving belt.The 4th instar (8-day-old) diamond-back moth larvae (Plu'tellamaculipennis), ten apterous (6- day-old) vetch aphids (Megoura viciae),and ten adult 1-2 week-old mustard beetles (Phaedon cochleariae)respectively were placed on the sprayed leaves and each plant thenenclosed in a glass cylinder fitted at one end with a muslin cap.Montality counts were made after 24 hours.

(IV) In tests against glass house red spider mites (Tetranychustelurius), lead discs cut from French bean plants were sprayed in themanner described under III. 1 hour after spraying, the discs wereinoculated with 10 adult mites. Mortality counts were made 24 hoursafter inoculation.

(V) In tests against large white butterfly larve (Pieris brassicae),cabbage leaves were sprayed in the manner described under III. 10 3rdinstar (*8-10 day-old) larvae were placed on discs cut from the sprayedleaves'within petri-dish pairs. Mortality counts were made 24 hoursafter inoculation.

The results of the above tests are summarized in Table 2 where A denotes100% kill, B partial kill and C no kill of tests insects. In Table 2compounds are indentibamoyl, .N-alkyl or N, N-'dia 1kylcarban l oylwherein each alkyl contains from 'l to6 carbon atoms, a hydrocarbongroup which is alkyl of 1 to 6 carbon atoms,cycloalkyl of 3 to 8 carbonatoms in the ring, aryl of 6 to wearbon atoms, aralkyl of 7 to" 9'carbon atoms, o r alkaryl of 7 to 9 carbon atoms or such hydrocarbongroup sub stituted by from one to a pluraity of halogen or cyanosubstituents; and R and which may be the same or different, are alkyl ofl to 6 carbon atoms, and an inert carrier. i

2. The insecticidal composition according to claim 1 'wherein R ishydrogen and R and R which may be the same or different, are alkylof 1-4carbon atoms.

3. The insecticidal composition according to claim 2 wherein X isoxygen.

4. The insecticidal composition according to claim 3 wherein R and'R areethyl. I

5. The insecticidal composition according to claim 2 wherein X issulfur.

6. The insecticidal composition according wherein R and R are methyl.

7. The insecticidal composition according to claimS wherein R is methyland R is butyl.

8. The insecticidal composition according'to claim 5 wherein R and R areethyl. 9. The insecticidal composition according to claim 5 wherein R ismethyl and R is isopropyl.

10. A method of combatting insects comprising apply ing to said insectsan insecticidally effective amount of a to claim 5 wherein X is oxygenor sulfur;- R is hydrogen; halogen,

cyano, alkoxycarbonyl of from 2 to 7 carbon atoms, carbamoyl, N-alkyl orN,N-dialkylcarbamoyl wherein each alkyl contains from 1 to 6 carbonatoms, a hydrocarbon group which is alkyl of 1-6 carbons, cycloalkyl of3 to fled in the same manner as in Table 1. 8 carbon atoms in the ring,aryl of 6 to 10 carbon atoms,

TABLE 2 Compound Insecticidal activity R R; R: X M.d. A.a. P.c. P.m.P.b. Mm. Ti.

H CH3 CH3 s A A A A A A- A E 02115 OZHE s A A A A A A A H CH: CH(CH3)2 sA A A A A A A H CH3 (oHmou; s A A A A A A A UN CH3 CH3 5 o o o A o A ACH3 CH3 5 B o A A 0 A A omoo 08H; CH CH3 s B A B o A A 01 OH; CH; s o Ao o B A CH3 CH3 CH3 8 A A A A A A (Ill) CH9 cm s A A A B A A (cHmt oncan 02H. 0 A A A A A l CH3 C2Hs CzHa O A A A A .AV

wherein X is oxygen or sulfur; R is hydrogen, halogen, cyano,alkoxycarbonyl of from 2 to 7 carbon atoms, cararalkylof 7 to 9 carbonatoms, or alkaryl of 7 to 9 carbon atoms or such hydrocarbon groupsubstituted by from one to a plurality of halogen or cyano substituents;and R and R which may be the same or different, are alkylof1-to-6.carbon atoms. 11. The methodof combatting insect's according toclaim 10 wherein R is hydrogen and R and R which may be the same ordifierent, are alkyl or 1-4 carbon atoms. i

12. The method of combatting insects according to claim 11 wherein X isoxygen. i

9 13. The method of combatting insects claim 12 wherein R and R areethyl.

14. The method of combatting insects claim 11 wherein X is sulfur.

15. The method of combatting insects claim 14 wherein R and R aremethyl.

16. The method of combatting insects claim 14 wherein R and R are ethyl.

17. The method of combatting insects claim 14 wherein R is methyl and Ris isopropyl.

18. The method of com'batting insects claim 14 wherein R is methyl and Ris butyl.

according to according to according to according to 10 References CitedUNITED STATES PATENTS 1/1963 McConnell et a1. 260302 1/ 1967 Schroeder260302 FOREIGN PATENTS 12/1964 Belgium 260302 8/ 1954 Great Britain260302 10 JERMOE D. GOLDBERG, Primary Examiner A. J ROBINSON, AssistantExaminer

